Tumor hypoxia has been implicated as a prognostic marker in human tumors and may be a determinant of tumor response to both radiation and cytotoxic therapy. We propose a pilot phase II clinical trial to determine the safety and feasibility of measurement of tumor hypoxia in patients with non-small cell lung cancer (NSCLC) using the 2-nitroimidazole, EF5. Specific Aim 1: Measurement of hypoxia in NSCLC by EF5 binding. Patients with Stage I/II or Stage III will be administered EF5 prior to surgical biopsy or excision of tumor. Tumor samples will be examined for binding of EF5 to hypoxic areas. Tumor response will be ascertained for those patients with Stage III disease receiving chemotherapy/radiation. Tumor samples will be obtained from patients undergoing repeat tumor biopsy to assess longevity of EF5 adducts. Hypothesis: There is a range of tumor hypoxia in NSCLC that can be detected by EF5 binding. Specific Aim 2: Correlation of hypoxia measured by EF5 with biological markers of hypoxia. Hypoxia induces a number of biological responses mediated through HIF-1-controlled expression. Concurrent measurement of potential serum markers of hypoxia, tissue protein markers of hypoxia, tumor angiogenesis, and apoptosis will be performed to allow correlation with measurement of tumor hypoxia. Hypothesis: Hypoxia measured by EF5 binding in tumor tissues is correlated with biological markers of hypoxia in tumor and blood of patients with NSCLC. Specific Aim 3: Correlate tumor perfusion as measured by clinically applicable methods with hypoxia in patients with non-small cell lung cancer. Tumor hypoxia results from altered tumor blood flow. Advances in imaging techniques allows the non-invasive measurement of tumor blood flow in patients. We will use 150-water PET scanning to measure tumor blood flow and correlate these measurements with tumor hypoxia and each other. Hypothesis: Altered (reduced) tumor blood flow is associated with greater tumor hypoxia. We believe the data from this pilot study will be useful to design future study(ies) with clinical endpoints and to guide selection of subjects for novel hypoxia-directed therapies in patients with NSCLC.